Genetically Engineered Skin Microbes Could Fuel Future Mosquito Repellents

Topical repellents are key to inhibiting mosquito attraction and limiting transmission of the deadly human pathogens they carry. Existing insect repellents, despite their potency, offer a short window of protection that leaves individuals open to exposure.

Now, researchers from the University of California, San Diego and Stanford University have genetically engineered human skin bacteria to make skin less attractive to mosquitoes.

Colonizing mice with the engineered bacteria reduced mosquito attraction and feeding for up to 11 uninterrupted days – considerably longer than the several hours of protection conferred by the leading chemical repellent.

The findings highlight how engineering the skin microbiome could be used to reduce disease-carrying insect attraction, preventing bites and virus transmission.

The results are published in the journal PNAS Nexus.

Creating a “living” repellent to outsmart mosquitoes

Mosquito-borne viral infections once confined to tropical regions are spreading. The Centers for Disease Control and Prevention reported that cases of dengue have doubled since just last year in the Americas, and warn of an increased risk of infection in the US.

Female mosquitoes on the hunt for blood rely on their acute olfactory system to detect volatiles and other specific odors released by skin microbes that live on their targets to locate their hosts. L-(+)-lactic acid is one of the most prominent mosquito-attracting volatiles from human emanation. It was recently discovered that many of these mosquito-attracting compounds, including L-(+)-lactic acid, are of bacterial origin.

In the present study, researchers engineered versions of the Staphylococcus epidermidis and Corynebacterium amycolatum bacteria, among the most abundant bacterial species on human skin. The researchers created strains deficient in L-(+)-lactic acid production through deletion of the L-lactate dehydrogenase gene.

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The authors tested the microbes in a culture-based high-throughput olfactometer assay and found the engineered version of S. epidermidis attracted about half as many Aedes aegypti and Anopheles gambiae mosquitoes and about 22% fewer Culex quinquefasciatus mosquitos as the wildtype (WT) versions of the microbes.

To examine these findings further in vivo, the researchers colonized mice with the engineered S. epidermidis. They found that colonizing the mice with WT S. epidermidis attracted mosquitoes while colonizing the mice with engineered S. epidermidis reduced mosquito attraction by up to 64.4%, with the effect lasting for 11 days. As observed for S. epidermidis, engineered C. amycolatum colonized mice showed reduced attraction to mosquitoes.

The engineered bacteria also affected mosquito feeding desire with a smaller proportion of the mosquitoes that landed on mice colonized with engineered microbes biting. This reduced feeding behavior was observed for seven consecutive days.

Engineering the skin microbiome

This study demonstrates the potent effect of human skin bacteria-derived L-(+)-lactic acid on mosquito attraction and feeding efficiency. The study presents engineering the skin microbiome to reduce attractive volatiles as an innovative untapped strategy to reduce vector attraction. The engineered microbes studied could offer a non-toxic, longer-lasting and less-smelly alternative to traditional repellents.

The next steps of this research will be determining if such L-(+)-lactic acid-deficient strains can colonize the human skin and compete against the WT microbiome.

The authors concluded, “Provided genetically engineered skin bacteria can grant effective and long-lasting reduced attraction to the human skin, this novel strategy could be used alone or in combination with topical application of synthetic repellents to reduce vectorial capacity and provide long-lasting skin protection from mosquito bites, pathogen transmission and mosquito-borne diseases.”

Reference: Liu F, Coutinho-Abreu IV, Raban R, et al. Engineered skin microbiome reduces mosquito attraction to mice. PNAS Nexus. 2024;3(7):pgae267. doi: 10.1093/pnasnexus/pgae267